LAIR1

Ideogram human chromosome 19

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is a protein that in humans is encoded by the LAIR1 gene. LAIR1 is a single-pass type I membrane protein that belongs to the immunoglobulin superfamily, more specifically to the inhibitory receptors subgroup. It is primarily expressed on the majority of immune system cells, including T lymphocytes, B lymphocytes, natural killer cells, monocytes, and dendritic cells. LAIR1 serves as an important regulator of the immune response, acting to maintain immune homeostasis and prevent excessive immune reactions.

Structure

LAIR1 is characterized by its extracellular domain, which contains a single immunoglobulin-like domain. This domain is responsible for the interaction with its ligands, which are primarily collagen molecules. The cytoplasmic tail of LAIR1 contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which, upon phosphorylation, recruit phosphatases such as SHP-1 and SHP-2. This recruitment leads to the downregulation of cell activation signals, thereby inhibiting immune cell activation.

Function

The primary function of LAIR1 is to act as an inhibitory receptor on immune cells. By binding to collagen, LAIR1 transmits inhibitory signals that dampen the immune response. This mechanism is crucial for preventing autoimmunity and maintaining tolerance to self-antigens. Additionally, LAIR1 plays a role in the regulation of immune cell proliferation, differentiation, and survival.

Clinical Significance

Alterations in LAIR1 expression or function have been implicated in various diseases, including chronic lymphocytic leukemia, rheumatoid arthritis, and other autoimmune diseases. Abnormal LAIR1 signaling can lead to either excessive immune responses, contributing to autoimmune pathology, or insufficient responses, which may result in increased susceptibility to infections and tumor growth.

Research Directions

Research on LAIR1 is focused on understanding its role in immune regulation and its potential as a therapeutic target. Strategies to modulate LAIR1 activity are being explored for the treatment of autoimmune diseases and cancer. For instance, blocking LAIR1 interaction with collagen has been proposed as a means to enhance immune responses against tumors.